rs4680

warrior vs worrier; number of other associations

Orientation

plus

Stabilized

plus

Geno	Mag	Summary
(A;A)	2.5	(worrier) advantage in memory and attention tasks
(A;G)		Intermediate dopamine levels, other effects
(G;G)	2.5	(warrior) multiple associations, see details

Reference

GRCh38 38.1/141

Chromosome

22

Position

19963748

Gene	COMT, MIR4761

is a	snp
is	mentioned by
dbSNP	rs4680
dbSNP (classic)	rs4680
ClinGen	rs4680
ebi	rs4680
HLI	rs4680
Exac	rs4680
Gnomad	rs4680
Varsome	rs4680
LitVar	rs4680
Map	rs4680
PheGenI	rs4680
Biobank	rs4680
1000 genomes	rs4680
hgdp	rs4680
ensembl	rs4680
geneview	rs4680
scholar	rs4680
google	rs4680
pharmgkb	rs4680
gwascentral	rs4680
openSNP	rs4680
23andMe	rs4680
SNPshot	rs4680
SNPdbe	rs4680
MSV3d	rs4680
GWAS Ctlg	rs4680

Merged from

Rs165688, Rs17849308

GMAF

0.3903

Max Magnitude

2.5

?	(A;A) (A;G) (G;G)	28

rs4680 (Val158Met) is a well studied SNP in the COMT gene. The COMT gene codes for the COMT enzyme, which breaks down dopamine in the brain's prefrontal cortex. The wild-type allele is a (G), coding for a valine amino acid; the (A) substitution polymorphism changes the amino acid to a methionine. This alters the structure of the resultant enzyme such that its activity is only 25% of the wild type. As a result, A allele carriers have more dopamine in their prefrontal cortex, which may be responsible for many of the neuropsychological associations listed below.

23andMe blog summarizes the alleles at this SNP as

• rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions
• rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions

Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis; summary at [PMID 17008817]) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compared with those with the Met substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.

Specific studies include:

rs4680, a functional Val/Met polymorphism, showed modest association with Irish familial schizophrenia. Haplotype A-G-A for SNPs rs737865-rs4680-rs165599 was preferentially transmitted to the affected subjects.

A study of 400 individuals reported that an increase in plasma total homocysteine (tHcy) of 10.4% (CI: 0.01-0.21, p=0.03) for associated with rs4680(A;A) homozygotes compared with rs4680(G;G) subjects. The (A;A) genotype was also more common, but statistically not that significantly, in venous thrombosis patients (OR 1.61, CI: 0.97-2.65], p=0.06) compared to control subjects.[PMID 18064318]

And from [PMID 15866551]: "Adolescent cannabis use was associated with increased risk of schizophreniform disorder in adulthood among Val/Val (i.e. rs4680(G;G)) individuals (OR = 10.9, 95% CI: 2.2–54.1) and, to a lesser extent, among Met/Val individuals (rs4680(A;G)); OR = 2.5, 95% CI: .78 – 8.2), but not among Met/Met (rs4680(A;A)) individuals (OR = 1.1, 95% CI: .21–5.4)."

Also potentially associated with schizophrenia

As part of a haplotype with rs4633, the (G) allele is also associated with endometrial cancer

In a study of 2 populations of breast cancer patients (2,000+ patients), increased risk was associated with rs4680(G;G) genotypes in both the Ontario [odds ratio 2.22, CI: 1.49-3.28] and Finland [OR 1.73, CI: 1.08-2.78] populations.[PMID 18194538]

23andMe blog The A version of rs4680 appears to boost working memory and cognitive function compared to G — but it also hampers emotional control.

[PMID 18704099] A study of 330 cocaine-dependent individuals, all of African descent, concluded that there was a slight (odds ratio 1.44, CI: 1.12-1.86, p = 0.014) association between the rs4680(A) allele, in other words the Met encoding allele, and cocaine dependence.

[PMID 18989660] A study of the antidepressant paroxetine found better response in Met/Met homozygotes, worse effects in Val/Val homozygotes and intermediate effects in heterozygotes. The effect became significant at the third week of treatment. Paroxetine daily dose was proportional to baseline severity, but did not influence outcome.

g2b2mh (A;A) subjects deploy more attentional focus when they realize they have made an error.

A meta-analysis of neuroimaging studies found a significant association between the COMT genotype and prefrontal activation; strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val).[PMID 19417742]

[PMID 19071221] gray matter volume and interacts with rs2097603 related to extracellular dopamine

[PMID 19207030] rs6275/DRD2 and rs4680/COMT useful in predicting disease risk among schizophrenia patients

[PMID 19037200] rs4680(G;G) carriers deprived of sleep respond quite well to 2x 100mg modafinil in terms of improved vigor and well-being, and maintained baseline performance with respect to executive functioning, whereas rs4680(A;A) individuals barely responded to the drug at all.

[PMID 16878403] Met158 allele carriers had "a more focused response...during a working memory task." "The met158 allele seems to be beneficial during the performance of working memory and attention-related tasks, whereas the val158 allele appears to be advantageous during the processing of aversive emotional stimuli."

[PMID 15673663] "Increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states."

[PMID 12595695] In response to pain Met/Met allele carriers showed greater "sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val158 homozygotes. The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli."

[PMID 20509070] Reports that ease of entering hypnosis correlates with number of rs4680(G) alleles.

see gs226 for a report related to impulsiveness

OMIM	116790
Desc	CATECHOL-O-METHYLTRANSFERASE POLYMORPHISM
Variant	0001
Related	also

[PMID 19367610] Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients

[PMID 19369177] Association of the 3' Region of COMT with Schizophrenia in Taiwan

[PMID 19417742] Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis

[PMID 19290789] Association studies of catechol-O-methyltransferase (COMT) gene with schizophrenia and response to antipsychotic treatment

[PMID 19077118] Genetic variants in COMT and neurocognitive impairment in families of patients with schizophrenia

OMIM	104300
Desc	ALZHEIMER DISEASE; AD
Variant
Related	also

[PMID 19474754] Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1

http://www.jneurosci.org/cgi/content/abstract/30/1/64 and blog discussion of data about rs4680 thinking about nothing in an fmri.

[PMID 19915868] Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines

[PMID 19946713] Attention-deficit/hyperactivity disorder phenotype is influenced by a functional catechol-O-methyltransferase variant

[PMID 20071037] Catechol-O-methyltransferase val108/158met genotype, major depressive disorder and response to selective serotonin reuptake inhibitors in major depressive disorder

[PMID 20070134] Association between COMT, PTSD, and increased smoking following hurricane exposure in an epidemiologic sample

[PMID 19690620] Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

[PMID 20150638] Association of COMT Haplotypes and Breast Cancer Risk in Caucasian Women

[PMID 20431430] The interaction between serotonin receptor 2A and catechol-O-methyltransferase gene polymorphisms is associated with the novelty-seeking subscale impulsiveness

[PMID 20488458] Heterozygosity at catechol-O-methyltransferase Val158Met and schizophrenia: New data and meta-analysis

[PMID 20934310] HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association

[PMID 20570835] No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain

[PMID 21084795] Acute Intravenous Synaptamine Complex Variant KB220™ "Normalizes" Neurological Dysregulation in Patients During Protracted Abstinence From Alcohol and Opiates as Observed Using Quantitative Electroencephalographic and Genetic Analysis for Reward Polymorphisms: Part 1, Pilot Study with 2 Case Reports

[PMID 21092186] Polymorphisms in genes involved in the estrogen pathway and mammographic density

[PMID 21120493] Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients

[PMID 21130573] COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia

[PMID 21191472] Genetic Association Between the COMT Genotype and Urinary Levels of Tea Polyphenols and Their Metabolites among Daily Green Tea Drinkers

[PMID 21300128] COMT Val158met variant and functional haplotypes associated with childhood ADHD history in women with bulimia nervosa

[PMID 10490706] Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype

[PMID 17949513] Association between a common haplotype in the COMT gene region and psychiatric disorders in individuals with 22q11.2DS

[PMID 21310591] Interaction between COMT haplotypes and cannabis in schizophrenia: A case-only study in two samples from Spain

[PMID 21449006] Role of COMT, 5-HT(1A) , and SERT genetic polymorphisms on antidepressant response to transcranial magnetic stimulation

[PMID 21567099] Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer

[PMID 21570824] Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids

[PMID 21595525] Sensory gating deficit is associated with catechol-O-methyltransferase polymorphisms in bipolar disorder

[PMID 21884617] Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults

[PMID 21934638] A COMT gene haplotype associated with methamphetamine abuse

[PMID 21940152] The impact of COMT gene polymorphisms on suicidality in treatment resistant major depressive disorder - A European Multicenter Study

[PMID 22067551] When control fails: Influence of the prefrontal but not striatal dopaminergic system on behavioural flexibility in a change detection task

[PMID 21947654] Cannabis, COMT and psychotic experiences

[PMID 22222175] COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes

[PMID 22337560] The COMT rs4680 Met allele contributes to long-lasting low back pain, sciatica and disability after lumbar disc herniation

[PMID 22417933] Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder

[PMID 22451510] Catechol-O-Methyltransferase Gene and Executive Function in Children With ADHD

[PMID 22479488] No Association of COMT (Val158Met) Genotype with Brain Structure Differences between Men and Women

[PMID 22475780] Association Between Val158Met Functional Polymorphism in the COMT Gene and Risk of Preeclampsia in a Chinese Population

[PMID 22528689] Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene

[PMID 22208661] A novel SNP in COMT is associated with alcohol dependence but not opiate or nicotine dependence : a case control study

[PMID 22178088] Catechol-O-methyltransferase (COMT) single nucleotide polymorphisms and haplotypes are not major risk factors for polycystic ovary syndrome

[PMID 22658813] Association Between Polymorphisms in COMT, PLCH1, and CYP17A1, and Non-Small-Cell Lung Cancer Risk in Chinese Nonsmokers

ClinVar
Risk	Rs4680(A;A)
Alt	Rs4680(A;A)
Reference	Rs4680(G;G)
Significance	Drug-response
Disease	CATECHOL-O-METHYLTRANSFERASE POLYMORPHISM nicotine response - Efficacy not specified
Variation	info
Gene	COMT MIR4761
CLNDBN	CATECHOL-O-METHYLTRANSFERASE POLYMORPHISM nicotine response - Efficacy not specified
Reversed	0
HGVS	NC_000022.10:g.19951271G>A
CLNSRC	OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)
CLNACC	RCV000019156.3, RCV000211145.1, RCV000244083.1,

[PMID 12802784] A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain.

[PMID 15098000] COMT haplotypes suggest P2 promoter region relevance for schizophrenia.

[PMID 15124004] Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families.

[PMID 15290009] Differential expression of human COMT alleles in brain and lymphoblasts detected by RT-coupled 5' nuclease assay.

[PMID 15457404] Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain.

[PMID 15505638] Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia.

[PMID 15931594] An entropy-based statistic for genomewide association studies.

[PMID 15956988] COMT polymorphisms and anxiety-related personality traits.

[PMID 16027741] Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease.

[PMID 16232322] COMT genetic variation confers risk for psychotic and affective disorders: a case control study.

[PMID 16380905] Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios.

[PMID 16380908] Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder.

[PMID 16395295] Significant association of catechol-O-methyltransferase (COMT) haplotypes with nicotine dependence in male and female smokers of two ethnic populations.

[PMID 16412218] Multilocus analysis of SNP and metabolic data within a given pathway.

[PMID 16453988] Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease.

[PMID 16483362] The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression.

[PMID 16574089] PCR screening for 22q11.2 microdeletion: development of a new cost-effective diagnostic tool.

[PMID 16786032] Impact of complex genetic variation in COMT on human brain function.

[PMID 16816420] Nonlinear tests for genomewide association studies.

[PMID 16816940] Direct molecular haplotyping of multiple polymorphisms within exon 4 of the human catechol-O-methyltransferase gene by liquid chromatography-electrospray ionization time-of-flight mass spectrometry.

[PMID 16837108] Haplotypes in cathechol-O-methyltransferase gene confer increased risk for psychosis in Alzheimer disease.

[PMID 16848906] Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans.

[PMID 17006672] Evidence for statistical epistasis between catechol-O-methyltransferase (COMT) and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of schizophrenia.

[PMID 17116718] Dietary phytoestrogen intake is associated with reduced colorectal cancer risk.

[PMID 17299513] Gender-dependent association of the functional catechol-O-methyltransferase Val158Met genotype with sensation seeking personality trait.

[PMID 17363961] Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment.

[PMID 17427186] Association analysis of COMT polymorphisms and schizophrenia in a Chinese Han population: a case-control study.

[PMID 17429315] Genetic polymorphisms in estrogen-metabolizing genes and breast cancer survival.

[PMID 17442488] An association study between cathechol-O-methyltransferase gene and mental retardation in the Chinese Han population.

[PMID 17466074] Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

[PMID 17482701] No associations exist between five functional polymorphisms in the catechol-O-methyltransferase gene and schizophrenia in a Japanese population.

[PMID 17483451] Gene-gene interaction associated with neural reward sensitivity.

[PMID 17504246] Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia.

[PMID 17604122] A quantitative association study between schizotypal traits and COMT, PRODH and BDNF genes in a healthy Chinese population.

[PMID 17630406] Dopamine genes and schizophrenia: case closed or evidence pending?

[PMID 17636223] Val153Met polymorphism of catechol-O-methyltransferase and prevalence of uterine leiomyomata.

[PMID 17707347] Genetic variation in catechol-O-methyltransferase: effects on working memory in schizophrenic patients, their siblings, and healthy controls.

[PMID 17961261] Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia.

[PMID 17994190] Norepinephrine transporter and catecholamine-O-methyltransferase gene variants and attention-deficit/hyperactivity disorder symptoms in adults.

[PMID 18081002] Association of catechol-O-methyltransferase variants with loudness dependence of auditory evoked potentials.

[PMID 18180394] Genetic variation within adrenergic pathways determines in vivo effects of presynaptic stimulation in humans.

[PMID 18196244] Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility.

[PMID 18213617] Putative role of the COMT gene polymorphism (Val158Met) on verbal working memory functioning in a healthy population.

[PMID 18235427] Catechol-O-methyltransferase (COMT) val158met genotype is associated with BOLD response as a function of task characteristic.

[PMID 18324659] COMT polymorphisms affecting protein expression are risk factors for endometrial cancer.

[PMID 18340529] A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk.

[PMID 18351593] DRD3, but not COMT or DRD2, genotype affects executive functions in healthy and first-episode psychosis adolescents.

[PMID 18384078] Association study of candidate variants of COMT with neuroticism, anxiety and depression.

[PMID 18389087] Rarity of Somatic Mutation and Frequency of Normal Sequence Variation Detected in Sporadic Colon Adenocarcinoma Using High-Throughput cDNA Sequencing.

[PMID 18408230] Structural cerebral variations as useful endophenotypes in schizophrenia: do they help construct "extended endophenotypes"?

[PMID 18436194] Catechol-O-methyltransferase contributes to genetic susceptibility shared among anxiety spectrum phenotypes.

[PMID 18444252] Neurotransmission and bipolar disorder: a systematic family-based association study.

[PMID 18466599] Linkage studies of catechol-O-methyltransferase (COMT) and dopamine-beta-hydroxylase (DBH) cDNA expression levels.

[PMID 18466879] Association of a nonsynonymous variant of DAOA with visuospatial ability in a bipolar family sample.

[PMID 18486967] A community-based study of cigarette smoking behavior in relation to variation in three genes involved in dopamine metabolism: Catechol-O-methyltransferase (COMT), dopamine beta-hydroxylase (DBH) and monoamine oxidase-A (MAO-A).

[PMID 18562342] Catechol-O-methyltransferase Val 158 Met polymorphism and antisaccade eye movements in schizophrenia.

[PMID 18574484] The complex global pattern of genetic variation and linkage disequilibrium at catechol-O-methyltransferase.

[PMID 18592033] Sex steroid-related candidate genes in psychiatric disorders.

[PMID 18628428] Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer.

[PMID 18698234] The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications.

[PMID 18715757] Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.

[PMID 18755576] Effect of COMT val158met genotype on cognition and personality.

[PMID 18787887] Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures.

[PMID 18802928] Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults.

[PMID 18805939] Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.

[PMID 18820009] Possible difference in frequencies of genetic polymorphisms of estrogen receptor alpha, estrogen metabolism and P53 genes between estrogen receptor-positive and -negative breast cancers.

[PMID 18929622] Dopamine 2 receptor C957T and catechol-o-methyltransferase Val158Met polymorphisms are associated with treatment response in electroconvulsive therapy.

[PMID 18937309] Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study.

[PMID 18988738] MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met.

[PMID 19074205] Drinking green tea modestly reduces breast cancer risk.

[PMID 19094200] Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain.

[PMID 19094875] [Effect of polymorphisms of the cathecol-O-methyltransferase on schizophrenia risk in a Spanish population].

[PMID 19127255] Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

[PMID 19174490] Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women.

[PMID 19197363] A genome-wide investigation of SNPs and CNVs in schizophrenia.

[PMID 19258022] Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.

[PMID 19287484] Clique-finding for heterogeneity and multidimensionality in biomarker epidemiology research: the CHAMBER algorithm.

[PMID 19329282] Meta-analysis of association between genetic variants in COMT and schizophrenia: an update.

[PMID 19359258] Cohort profile: risk patterns and processes for psychopathology emerging during adolescence: the ROOTS project.

[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.

[PMID 19520435] Acute antidepressant response to sleep deprivation combined with light therapy is influenced by the catechol-O-methyltransferase Val(108/158)Met polymorphism.

[PMID 19545856] Sensorimotor gating depends on polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase, but not on neuregulin-1 Arg38Gln genotype: a replication study.

[PMID 19578924] The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis.

[PMID 19582565] Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder.

[PMID 19584770] Variants in COMT and spontaneous smoking cessation: retrospective cohort analysis of 925 cessation events.

[PMID 19647329] COMT val(158)met genotype and smooth pursuit eye movements in schizophrenia.

[PMID 19664744] A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease.

[PMID 19693005] Executive function, neural circuitry, and genetic mechanisms in schizophrenia.

[PMID 19693267] Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene.

[PMID 19721400] Association between COMT gene and Chinese male schizophrenic patients with violent behavior.

[PMID 19852950] The association of catechol-O-methyltransferase genotype with the phenotype of women with eating disorders.

[PMID 19911060] Persistence criteria for susceptibility genes for schizophrenia: a discussion from an evolutionary viewpoint.

[PMID 19940176] Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans.

[PMID 20122740] Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar disorder.

[PMID 20148275] Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

[PMID 20179754] Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

[PMID 20191112] The Genetics of Anorexia Nervosa: Current Findings and Future Perspectives.

[PMID 20205808] Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients.

[PMID 20483479] Analysis of association between the catechol-O-methyltransferase (COMT) gene and negative symptoms in chronic schizophrenia.

[PMID 20531207] The impact of catechol-O-methyltransferase SNPs and haplotypes on treatment response phenotypes in major depressive disorder: a case-control association study.

[PMID 20565774] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

[PMID 20627703] The association of single nucleotide polymorphisms in the catechol-O-methyltransferase gene and pain scores in female patients with major depressive disorder.

[PMID 20667552] Catechol-o-methyltransferase gene modulation on suicidal behavior and personality traits: review, meta-analysis and association study.

[PMID 20728009] Association between Novelty Seeking of opiate-dependent patients and the catechol-O-methyltransferase Val(158)Met polymorphism.

[PMID 20863768] Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.

[PMID 20878621] Impact of CYP1A1 and COMT genotypes on breast cancer risk in Mexican women: a pilot study.

[PMID 20979431] Polymorphisms of COMT and XPD and risk of esophageal squamous cell carcinoma in a population of Yili Prefecture, in Xinjiang, China.

[PMID 21059181] Polymorphisms of adrenergic cardiovascular control genes are associated with adolescent chronic fatigue syndrome.

[PMID 21106664] Association of COMT Val(108/158)Met genotype and cigarette smoking in pregnant women.

[PMID 21144097] The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract.

[PMID 21162693] Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction.

[PMID 21172166] Pharmacogenetics of antidepressant response.

[PMID 21215384] Interactive effects of DAOA (G72) and catechol-O-methyltransferase on neurophysiology in prefrontal cortex.

[PMID 21216270] Role of gene-gene/gene-environment interaction in the etiology of eastern Indian ADHD probands.

[PMID 21300759] EGFR L858R mutation and polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients.

[PMID 21304959] Epistasis between COMT and MTHFR in maternal-fetal dyads increases risk for preeclampsia.

[PMID 21330274] Pharmacogenetics of smoking cessation in general practice: results from the patch II and patch in practice trials.

[PMID 21355050] A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2).

[PMID 21356266] Interactions between the COMT Val108/158Met polymorphism and maternal prenatal smoking predict aggressive behavior outcomes.

[PMID 21423693] Effect sizes in experimental pain produced by gender, genetic variants and sensitization procedures.

[PMID 21445667] Variation in genes involved in dopamine clearance influence the startle response in older adults.

[PMID 21462137] [An association study of COMT gene polymorphisms with schizophrenia].

[PMID 21486391] The association between catechol-O-methyl-transferase Val108/158Met polymorphism and suicide.

[PMID 21495799] COMT polymorphism and the risk of endometriosis-related infertility.

[PMID 21508242] Dopaminergic genes predict individual differences in susceptibility to confirmation bias.

[PMID 21600957] COMT and age at onset in mood disorders: a replication and extension study.

[PMID 21609749] Role of functional dopaminergic gene polymorphisms in the etiology of idiopathic intellectual disability.

[PMID 21656904] Association between polymorphisms in catechol-O-methyltransferase (COMT) and cocaine-induced paranoia in European-American and African-American populations.

[PMID 21776034] Association of the catechol-O-methyl transferase gene Val158Met polymorphism with blood pressure and prevalence of hypertension: interaction with dietary energy intake.

[PMID 21895373] Psychological distress in fibromyalgia patients: a role for catechol-O-methyl-transferase Val158met polymorphism.

[PMID 21999147] Diverse facets of COMT: from a plausible predictive marker to a potential drug target for schizophrenia.

[PMID 22024485] Genetic associations with performance on a behavioral measure of distress intolerance.

[PMID 22259185] Additive effects of serotonergic and dopaminergic polymorphisms on trait impulsivity.

[PMID 22293393] Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity.

[PMID 22349272] Age modulates the effect of COMT genotype on delay discounting behavior.

[PMID 22366815] Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data.

[PMID 22466345] Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.

[PMID 22487365] C957T polymorphism of the dopamine D2 receptor gene is associated with motor learning and heart rate.

[PMID 22530780] Impact of five SNPs in dopamine-related genes on executive function.

[PMID 22963606] No association of catechol-o-methyltransferase polymorphisms with schizophrenia in the han chinese population

[PMID 22615781] Candidate gene-based association study of antipsychotic-induced movement disorders in long-stay psychiatric patients: a prospective study

[PMID 22978509] Convergence of Genome-Wide Association and Candidate Gene Studies for Alcoholism

[PMID 22707271] The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion

[PMID 23141115] The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder

Breast Cancer Risk Modifiers

[PMID 22790479] Association of COMT gene polymorphisms with systemic atherosclerosis in elderly Japanese

[PMID 22612913] Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study

[PMID 23269216] Association between the COMT gene and rumination in a Hungarian sample

[PMID 23278923] The COMT Val/Met polymorphism is associated with reading-related skills and consistent patterns of functional neural activation

[PMID 23288874] Lack of Association of a Functional Catechol-O-Methyltransferase Gene Polymorphism With Risk of Tobacco Smoking: Results From a Multicenter Case-Control Study

[PMID 23370603] Catechol-O-Methyltransferase and Cytochrome P-450 1B1 Polymorphisms and Endometrial Cancer Risk: A Meta-analysis

[PMID 23369671] Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study

[PMID 23440431] Association of the COMT Met158 allele with trait impulsivity in healthy young adults

[PMID 23515273] Playing nice: a multi-methodological study on the effects of social conformity on memory

[PMID 23715639] The association between the catechol-O-methyltransferase Val108/158Met polymorphism and hyperactive-impulsive and inattentive symptoms in youth

[PMID 23728717] Common functional polymorphisms in SLC6A4 and COMT genes are associated with circadian phenotypes in a South American sample

[PMID 23785672] Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

[PMID 23798967] No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

[PMID 23353103] COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study

[PMID 23840506] Multivariate analysis of dopaminergic gene variants as risk factors of heroin dependence

[PMID 23880798] No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women

[PMID 23928748] Impact of COMT genotype on serotonin-1A receptor binding investigated with PET

[PMID 23941313] Influence of a Dopamine Pathway Additive Genetic Efficacy Score on Smoking Cessation: Results from Two Randomized Clinical Trials of Bupropion

[PMID 24167357] COMT-Val158Met-Polymorphism Is Not a Risk Factor for Acute Kidney Injury after Cardiac Surgery

[PMID 24320736] Role of single nucleotide polymorphisms in estrogen-metabolizing enzymes and susceptibility to uterine leiomyoma in Han Chinese: A case-control study

[PMID 24382678] Association between maternal COMT gene polymorphisms and fetal neural tube defects risk in a Chinese population

[PMID 24399714] BDNF rs 6265 polymorphism and COMT rs 4680 polymorphism in deficit schizophrenia in Polish sample

[PMID 24407958] Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures

[PMID 24448899] Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype

[PMID 24499375] Association of Oxidative Stress Related Genes with Idiopathic Recurrent Miscarriage

[PMID 23706899] Catechol-O-methyltransferase genotype as modifier of superior responses to venlafaxine treatment in major depressive disorder

[PMID 24575113] Association between the COMTVal158Met Genotype and Alzheimer's Disease in the Han Chinese Population

[PMID 22021659] Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.

[PMID 22683321] Epistatic interactions implicating dopaminergic genes in bulimia nervosa (BN): relationships to eating- and personality-related psychopathology.

[PMID 22713126] COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder.

[PMID 22718527] The associations between OPRM 1 and COMT genotypes and postoperative pain, opioid use, and opioid-induced sedation.

[PMID 22722321] Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis.

[PMID 22763378] Increased corpus callosum volume in children with chromosome 22q11.2 deletion syndrome is associated with neurocognitive deficits and genetic polymorphisms.

[PMID 22784685] The COMT Met158 allele and violence in schizophrenia: a meta-analysis.

[PMID 22841130] Shared and unique genetic contributions to attention deficit/hyperactivity disorder and substance use disorders: a pilot study of six candidate genes.

[PMID 22890010] Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

[PMID 22890094] Influence of COMT Val158Met polymorphism on Alzheimer's disease and mild cognitive impairment in Italian patients.

[PMID 22900954] COMT val158met predicts reward responsiveness in humans.

[PMID 22901597] Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.

[PMID 23000097] Polymorphisms of catechol estrogens metabolism pathway genes and breast cancer risk in Mexican women.

[PMID 23008195] Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: relevance for major depression.

[PMID 23069674] No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias.

[PMID 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.

[PMID 23178897] The catechol-O-methyltransferase gene (COMT) and cognitive function from childhood through adolescence.

[PMID 23219927] Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism.

[PMID 23261162] DBH -1021C>T and COMT Val108/158Met genotype are not associated with the P300 ERP in an auditory oddball task.

[PMID 23302985] The effect of OPRM1 and COMT genotypes on the analgesic response to intravenous fentanyl labor analgesia.

[PMID 23351565] Potential role of membrane-bound COMT gene polymorphisms in female depression vulnerability.

[PMID 23408064] The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism.

[PMID 23421762] COMT rs4680 Met is not always the 'smart allele': Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese.

[PMID 23618651] Effect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder.

[PMID 23733030] Pharmacogenetics in major depression: a comprehensive meta-analysis.

[PMID 23773341] An opposite-direction modulation of the COMT Val158Met polymorphism on the clinical response to intrathecal morphine and triptans.

[PMID 23774690] Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population.

[PMID 23818048] Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

[PMID 24593143] Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children

[PMID 24763183] Catechol-O-methyltransferase Val158-Met polymorphism and a response of hyperactive-impulsive symptoms to methylphenidate: A replication study from South Korea

[PMID 24777039] A Multicenter Case-Control Study on Screening of Single Nucleotide Polymorphisms in Estrogen-Metabolizing Enzymes and Susceptibility to Uterine Leiomyoma in Han Chinese

[PMID 24819480] COMT gene and risk for Parkinson's disease: a systematic review and meta-analysis

[PMID 24853458] Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects

[PMID 23598060] Association study of polymorphisms in the alpha 7 nicotinic acetylcholine receptor subunit and catechol-o-methyl transferase genes with sensory gating in first-episode schizophrenia

[PMID 25013436] The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta-Analysis

[PMID 25029900] Interactive effects of the COMT gene and training on individual differences in supervisory control of unmanned vehicles

[PMID 25038551] Dopamine system genes are associated with orienting bias among healthy individuals

[PMID 25063767] Interactions Between Early Trauma and Catechol-O-Methyltransferase Genes on Inhibitory Deficits in Children With ADHD

[PMID 25161818] The influence of COMT Val(158)Met genotype on the character dimension cooperativeness in healthy females

[PMID 24274352] Green tea consumption and breast cancer risk in Japanese women: a case-control study

[PMID 25218601] Epistasis Between Polymorphisms in COMT, ESR1, and GCH1 Influences COMT Enzyme Activity and Pain

[PMID 24225542] Association of COMT val158met and DRD2 G>T genetic polymorphisms with individual differences in motor learning and performance in female young adults

[PMID 25292091] Lack of Association between the COMT rs4680 Polymorphism and Ovarian Cancer Risk: Evidence from a Meta-analysis of 3,940 Individuals

[PMID 25491588] Association between the catechol-O-methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population

GWAS snp
PMID	[PMID 24816252]
Trait	Blood metabolite levels
Title	An atlas of genetic influences on human blood metabolites.
Risk Allele	A
P-val	5E-178
Odds Ratio	.05 [0.045-0.053] unit decrease

[PMID 24862404] Exploring the indirect effects of catechol-O-methyltransferase (COMT) genotype on psychotic experiences through cognitive function and anxiety disorders in a large birth cohort of children

[PMID 24495967] Common polymorphisms in dopamine-related genes combine to produce a 'schizophrenia-like' prefrontal hypoactivity

[PMID 25805645] Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease

[PMID 25927430] Association of DRD3, COMT, and SLC6A4 Gene Polymorphisms with Type 2 Diabetes in Southern Chinese: A Hospital-Based Case-Control Study

[PMID 26026741] Lack of association between COMT polymorphism rs4680 and risk of Alzheimer׳s disease in Asians: Evidence from a meta-analysis

[PMID 26053146] Child Exposure to Serious Life Events, COMT, and Aggression: Testing Differential Susceptibility Theory

[PMID 25184405] Subclinical psychotic experiences in healthy young adults: associations with stress and genetic predisposition

[PMID 25636089] [Polymorphisms of catechol-O-methyltransferase and monoamine oxidase B genes among Chinese patients with Parkinson's disease]

[PMID 26253436] Relationship between the catechol-O-methyl transferase Val108/158Met genotype and brain volume in treatment-naive major depressive disorder: Voxel-based morphometry analysis

[PMID 26489634] Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients

[PMID 26508970] Association of the Catechol O-Methyltransferase Val158-Met Polymorphism and Reduced Interference Control in Korean Children with Attention-Deficit Hyperactivity Disorder

[PMID 26849490] Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study.

[PMID 26973509] Pulse Pressure Magnifies the Effect of COMT Val(158)Met on 15 Years Episodic Memory Trajectories.

[PMID 27091610] COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.

[PMID 27103528] Association of genetic risk factors with cognitive decline: the PATH through life project.

[PMID 27228319] A Tetra-Primer Amplification Refractory System Technique for the Cost-Effective and Novel Genotyping of Eight Single-Nucleotide Polymorphisms of the Catechol-O-Methyltransferase Gene.

[PMID 28273278] Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

[PMID 28451382] Roles of functional catechol-O-methyltransferase genotypes in Chinese patients with Parkinson's disease.

[PMID 29325115] Higher Fast sleep spindle density in rs4680(A;A) (Met, n=39) than rs4680(G;G) (Val, n=39) and rs4680(A;G, n=72) (Met/Val), i.e. genotype of Catechol-O-Methyltransferase (COMT), every rs4680(G) reduced fast sleep spindles. Slow spindle density in heterozygote subjects rs4680(A;G) was lower than that of both homozygote groups (rs4680(A;A) or rs4680(G;G)). Morphological characteristics of fast and slow spindles did not show significant differences between genotypes. COMT genotype had also no significant effect on measures of general sleep quality.

[PMID 29559808] Association of genetic variation in COMT gene with pain related to sickle cell disease in patients from the walk-PHaSST study.

[PMID 29578580] MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson's Disease.

[PMID 30011860] Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease.

[PMID 29330410] The Impact of COMT and Childhood Maltreatment on Suicidal Behaviour in Affective Disorders.

[PMID 31874497] [Effect of opioid-related gene polymorphisms on patients with high-dose opioid-tolerant cancer pain].

[PMID 32185238] Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia.

[PMID 32433545] Cannabinoid receptor CNR1 expression and DNA methylation in human prefrontal cortex, hippocampus and caudate in brain development and schizophrenia.

[PMID 32525059] Genetic underpinnings of schizophrenia-related electroencephalographical intermediate phenotypes: A systematic review and meta-analysis.

[PMID 32976278] Correlation Between the Warrior/Worrier Gene on Post Burn Pruritus and Scarring: A Prospective Cohort Study.

[PMID 33451866] Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery.

[PMID 33588721] Risk Genes in Schizophrenia and Their Importance in Choosing the Appropriate Antipsychotic Treatment.